tbuckley/cabot-search huggingface dataset:
A phase II study to evaluate the efficacy and safety of combination therapy of durvalumab (MEDI4736) and amrubicin in patients with recurrent small cell lung cancer (SCLC): Aphrodite trial, in progress.
Authors: Yuka Kato, Kadoaki Ohashi, Toshiyuki Kozuki, Shoichi Kuyama, Kakuhiro Yamaguchi, Toshihide Yokoyama, Hideki Uno, Michihiro Yoshida, Noboru Hattori, Katsuyuki Hotta, Katsuyuki Kiura
Journal: Journal of Clinical Oncology (2023)

TPS8612 Background: Immunochemotherapy (ICT) is the standard first-line treatment for extensive stage (ES)-SCLC. However, progression-free survival for patients (pts) treated with ICT as first-line therapy is approximately 5 months, and half of the pts will relapse within 6 months. Several drugs have been approved for the treatment after relapse, and amrubicin has been used as a second-line treatment in Japan for 20 years. However, the efficacy of pts treated with amrubicin is unsatisfactory, the median survival was 9.2 months (pts with sensitive relapse (SR-pts)) and 2.6 months (pts with refractory relapse (RR-pts)), indicating an urgent need for new therapeutic strategies in the treatment of post-relapse SCLC pts. A retrospective study showed significant improvement in survival for patients who progress on immunochemotherapy, treated with same ICI plus chemotherapy as second-line therapy (Trans Lung Cancer Rec. 2020). Cytotoxic chemotherapy introduced immunogenic cell death and the addition of chemotherapy to ICI might have a synergistic effect. Based on these assumptions, the combination of amrubicin with ICI may provide additional benefit for post-progression pts and we are therefore initiating this study. Methods: This is an open-label, single-arm, multicenter, physician-initiated Phase 2 study of amrubicin plus durvalumab in Japanese pts with relapsed SCLC. The study is divided into a lead-in cohort (LIC) and a Phase 2 part; the LIC will use a 3+3 design to ensure safety and will proceed to the Phase 2 part if the first 3 pts have no dose limiting toxicity (DLT) or the first 6 pts have only 1 DLT. Eligibility criteria include pts with ES-SCLC who relapse after platinum-containing chemotherapy with durvalumab as first-line therapy, age ≥20, ECOG 0-1. The primary endpoint is 1-year survival. Patients were treated with intravenous amrubicin 40 mg/m2 on day 1-3 and durvalumab 1500 mg/body on day 1 every 3 weeks until PD or unacceptable toxicity. The planned number of pts was 18 each with sensitive relapse (SR-pts) and refractory relapse (RR-pts) which was calculated based on the results of a previous randomized controlled trial (J Clin Oncol. 2008). In this trial, the point estimates and two-sided 90% confidence intervals (Clopper Peason method) for 1-year survival corresponding to the expected 1-year survival were: SR-pts (11/18 patients): 0.611 (90% CI: 0.392-0.801), RR-pts (8/18 0.444 (90% CI: 0.244-0.659). Enrollment began in October 2022, and will be completed by March 2025. Clinical trial information: jRCT2061220036 .
Patient characteristics associated with psychosocial distress about end-of-life.
Authors: Ana Isabel Tergas, Marianne Razavi, Matthew J. Loscalzo, Xiomara Rocha-Cadman, Paul K. Maciejewski, Holly Gwen Prigerson, Karen L. Clark
Journal: Journal of Clinical Oncology (2023)

12031 Background: A cancer diagnosis and subsequent treatment can cause significant psychosocial distress, including fear about the end of life (EoL). Although distress is common, it often goes unrecognized due to the challenge of routine psychosocial distress screening. This study sought to determine patient characteristics associated with EoL-related distress. Methods: A validated psychosocial distress screening tool (SupportScreen) was administered to patients prior to treatment at an NCI-designated cancer center between 2009-2017. Fear about EoL was measured on a 5-point Likert scale with scores of ≥3 indicating “high” distress. Multivariable logistic regression was used to test the association between fear of Eol and patients’ characteristics (age, sex, education, household income, survey language, race/ethnicity, and cancer diagnoses). Pairwise comparisons were run for cancer types and p-values were adjusted. Results: A total of 4,198 patients with cancer were included. Of these, 21.5% reported high distress from fear about EoL. Most patients were women (61%) and non-Latino white (60%). The average age was 59.9 years (SD = 13.9). About 29% of the participants had household income &lt; $40,000. The most common cancers in this sample were breast (22%), hematological (15%), gastrointestinal (14%) and gynecological (13%). Adjusted analyses showed that being a woman (OR = 1.30, p &lt; 0.042), taking the survey in Spanish (OR = 1.71, p = 0.020) and having a household income &lt; $40,000 (OR = 1.80, p &lt; 0.001) were all associated with high distress for EoL. Among cancer types, lung cancer (versus breast, digestive, gynecological, hematological, and prostate cancers) was significantly linked to high distress (p-values &lt; 0.05). Conversely, older age (OR = 0.99, p = 0.009) was associated with low distress. Conclusions: In this study, we identified patient clinical and demographic characteristics associated with high levels of distress due to fear of EoL. Patients who have lower household income, limited English proficiency, are younger, and female, as well as patients with lung cancer, may benefit from targeted screening for EoL distress, to facilitate early identification and tailored supportive care assistance.
Safety, tolerability, and quality of life (QoL) of single-agent plinabulin (Plin) for the prevention of docetaxel (Doc) chemotherapy (chemo)-induced neutropenia (CIN) in non-small cell lung cancer (NSCLC) patients (pts) from two randomized trials.
Authors: Douglas W. Blayney, Gabrielle Legaspi, Stephen Duprez, Lan Huang, Ramon W. Mohanlal
Journal: Journal of Clinical Oncology (2023)

e21168 Background: Plin, is a novel, non-G-CSF, small molecule agent with comparable CIN-preventive effects vs pegfilgrastim. In contrast to pegfilgrastim, Plin is given on the same day of chemo (30 mins after chemo), and does not cause bone pain, nor thrombopenia. In the two randomized controlled (placebo (Plac)/no treatment) cancer trials, Phase (Ph) 2 Study 101 and Ph3 Study 103, single-agent (SA) Plin reduced estimated Doc-induced mean duration of severe neutropenia by &gt; 1 Day vs Plac. We conducted a post hoc analysis of safety, tolerability, and QoL in NSCLC pts from these trials. Methods: NSCLC pts in 2 nd /3 rd line, with at least 1 NCCN FN risk factor, were randomized to Doc (75 mg/m 2 ) + Plin (n = 116; at the CIN dose of 20 mg/m 2 or its pharmacokinetic equivalent), or Doc + Plac (n = 296) in trials 101 (NCT00630110) and 103 (NCT02504489). Doc was given on day (D) 1, and Plin was given twice per cycle, on D1 and D8 (Plin D1 and D8 dosing is supratherapeutic for CIN but facilitated a more robust safety/tolerability evaluation [the CIN Plin dose is D1 only]). Safety blood draws and AE collection on D1 and D8; tolerability; and QoL (pre-dose and D8) were evaluated over 4 cycles. All pts received dexamethasone premedication. QoL scores were obtained in study 103 only, with Plin (n = 80) and Plac (n = 234), by validated questionnaires (EORTC QLQ C30, to evaluate global health status/QoL; the combined symptom scales/items, and the lung cancer-specific QoL questionnaire QLQ-LC13). Results: QoL scores over 4 cycles between Plin and Plac were similar, indicating Plin was well-tolerated. Grade (Gr) 3/4 AEs of interest for Plin (+Doc) and Plac (+Doc) are summarized in the table. With Plin, AE frequency of diarrhea was slightly higher (5.2% vs 1%; 1 Gr4 case with Plin), but was manageable, and so was hypertension (11.2% vs 1.7%; all Gr3 cases) vs Plac. Hypertension occurred around the time of infusion and was short-lasting (~2-4 hours) and typically self-limiting. Plin had less AEs of neutropenia (16.4% vs 50.3%) and leukopenia (15.5% vs 38.5%) vs Plac. Conclusions: Plin is an effective agent for CIN, has a favorable safety, tolerability, and QoL profile, and has the advantage of dosing on the same day of chemo. Clinical trial information: NCT02504489 . [Table: see text]
Workplace sexual harassment in academic oncology.
Authors: Divya Yerramilli, Vonetta Michelle Williams, Sankalp Pandya, Valerie M Dandar, Bismarck Odei, Fumiko Chino
Journal: Journal of Clinical Oncology (2023)

11003 Background: Research has shown workplace sexual harassment (WSH) is a pervasive problem in academia, affecting recruitment, retention &amp; career advancement of women faculty. This study examines WSH in academic oncology faculty in a national survey. Methods: We obtained data from the Association of American Medical Colleges StandPoint Faculty Engagement Survey between 2020-22 representing a national sample of academic faculty from 25 medical schools (overall response rate (RR) 58%). WSH was considered specific “unwanted behavior” by coworkers that occurred at least once in the past year. Reporting questions were asked on a 5-point Likert Scale from Strongly Disagree to Strongly Agree, with 6 th option “I Don’t Know.” Responses were grouped as Agree/Strongly Agree vs all others. Chi-square tested for differences by gender and race/ethnicity. Results: 807/1,287 oncologists participated in the survey (RR 63%), and 91% (731) answered the WSH questions. Most self-identified as men (58%) and only 8% identified as underrepresented race/ethnicity (URiM). See Table for findings. In oncology, women experienced any WSH at higher rates than men (33.1% vs 10.3%, p=0.001). The most common was derogatory comments due to gender. Regardless of gender, most knew how to report WSH incidents, but men were more likely to feel safe reporting. While 64.9% of men felt confident that their medical school would resolve WSH incident(s) effectively, only 48.7% of women did. Positive perceptions of reporting decrease among those who reported harassment. URiM faculty (35.6% vs.18.5%, p=0.001) were more likely than non-URiM faculty to experience at least one of the five harassment behaviors, although this was limited by small sample. Conclusions: In academic oncology, women and URiM experience workplace sexual harassment more often than men and non-URiM. Less than half of women felt confident that reporting an incident would lead to effective resolution. Urgent intervention is needed to combat the negative force of sexual harassment on workforce equity. [Table: see text]
Molecular pathways involved in hepatoblastoma tumorigenesis in trisomy 18.
Authors: Emily Schepers, Kathryn Glaser, Harrison Zwolshen, Alexander Bondoc
Journal: Journal of Clinical Oncology (2023)

e22015 Background: Trisomy 18 (T18) is the second most common aneuploidy caused by additional copies of chromosome 18. It occurs at a rate of 1 in 2000-6000 live births, with current 1-year survival rates between 5-10% of live births. Meta-analysis of tumor in T18 patients revealed 67 tumors, with 44 (66%) being HB. The contribution of underlying genetic alterations to tumorigenesis is incompletely understood. There is a reversed gender ratio in children with T18 and HB as well as more favorable histology and response to treatment. These suggest an alternative molecular pathway in these cases might promote tumorigenesis. Although there is an association between trisomy 18 and hepatoblastoma, the cause of this increased incidence is unknown. We hypothesize that SMAD4/TGFβ signaling in conjunction with canonical Wnt signaling has a role in T18 HB tumor development as well as a more fetal tumor histology. Methods: Seven patients with T18 were treated at CCHMC for HB. Five patient samples were collected at time of surgery for evaluation. Patient samples and data were collected with informed consent and institutional IRB approval. We performed transcriptomic analysis using RNA bulk sequencing data for five paired background and tumor samples. Further gene and protein expression were evaluated and compared to non-syndromic patients with HB. Histologic evaluation for tumor subtype and target proteins was performed. Results: Of the seven patients evaluated, six (85.7%) were female with a median age of diagnosis of 9 months. All patients underwent hepatectomy, with final pathology demonstrating predominantly fetal histology. All patients are currently in remission. Bulk RNAseq demonstrated upregulation of SMAD4 and TGFβ, as well as upregulation of canonical Wnt signaling pathway including Wnt3 and transcription factors Lef1, TCF4, and APC in tumor of T18 patients compared to background and non-syndromic HB patients. β-catenin immunostaining demonstrates increased or stabilized expression in tumor compared to background liver consistent with non-syndromic HB. Conclusions: We have identified a novel tumorigenic mechanism of HB in T18. Upregulation of SMAD4 in T18 results in increased TGFβ signaling, with potential crosstalk between SMAD4/TGFβ and Wnt/β-catenin signaling promoting cancer development. Further evaluation is required to understand the pathway crosstalk and impact of genetic mutation on pathway regulation.
Survivorship in patients with cardiac metastases defined by cardiac magnetic resonance imaging in relation to lesion hypoperfusion.
Authors: Raina Jain, Nicole Liberman, Hannah Agoglia, Michael Park, Robert Park, Jose Jessurun, William D. Tap, Jiwon Kim, Richard Steingart, Jennifer Liu, Jonathan W. Weinsaft, Angel Chan
Journal: Journal of Clinical Oncology (2023)

e24070 Background: Cardiac metastases (C MET ) can occur in late-stage cancer, but limited data exists on prognostic implications in context of current day cancer care. Cardiac magnetic resonance imaging (CMR) provides a new, well validated, means to identify C MET in vivo, and assess magnitude of lesion vascularity – which can vary in relation to tumor etiology and be compromised with tumor necrosis. Survivorship in pts with C MET and modifying impact of lesion vascularity are unknown. Methods: The population comprised adult (≥18yo) pts with metastatic cancer derived from a dual site CMR registry, including pts with and without C MET on CMR. CMR was performed via a uniform protocol for which C MET was defined using established criteria as a cardiac mass with late gadolinium enhancement; lesion vascularity was measured on perfusion-CMR. Cancer type was categorized by pathological review and follow-up was performed for all-cause mortality. Results: 330 pts (59±15 yo; 55% M) were studied, inclusive of C MET and controls matched for cancer etiology/stage. Among pts with C MET , cancer etiology varied (sarcoma 24% | GI 18% | GU 13% | lymphoma 13% | lung 10% | skin/melanoma 7% |); cases and controls were similar with respect to age, sex, anti-cancer regimen, and cardiac function on CMR (all p = NS). Median duration of post-CMR follow-up was 19 months [IQR 11.9 – 43.6]; 92% had clinical follow-up ≥ 1 year or mortality within this interval, including an aggregate 1-year mortality in pts with C MET of 53% (43% in C MET - controls; p = 0.09). Among cancer categories, pts with lymphoma were at decreased risk for death (HR 0.44 [0.26 – 0.75], p = 0.002); risk was increased in pts with GI malignancies (1.63 [1.12 – 2.37], p = 0.01) or those treated with antimetabolites or kinase inhibitors (both p &lt; 0.05): Neither age, sex, cardiac risk factors nor function granted increased risk for death (all p = NS). Regarding C met tissue characteristics, decreased lesion perfusion conferred increased mortality risk irrespective of whether assessed as a continuous variable (HR 1.29 [1.08 – 1.56]) or via graded tertiles (HR 1.32 [1.05 – 1.66]) of hypoperfusion (both p &lt; 0.05). Decreased C MET perfusion conferred increased mortality risk (1.30 [1.03 – 1.64], p = 0.03) independent of cancer type or anticancer regimen. Conclusions: Among systemic cancer pts with C MET , survivorship varies and nearly half are alive ≥1 year post cardiac MRI diagnosis. Prognosis in pts with C MET varies inversely to lesion perfusion, with low vascularity lesions conferring increased mortality risk.[Table: see text]
A national analysis of demographic trends in gynecological cases of basosquamous carcinoma.
Authors: Jaylin Tuman, Beau Hsia, Darby Keirns, Augustus Malan, Peter T. Silberstein, Xinxin Wu
Journal: Journal of Clinical Oncology (2023)

e21598 Background: Basosquamous carcinoma (BSC) is an aggressive form of basal cell carcinoma. Research on BSC is minimal because of its rare nature and the lack of clinical features that distinguish BSC from other forms of basal cell carcinoma, meaning that a diagnosis is only confirmed following biopsy. BSC is distinct because it has features of squamous cell carcinoma, making it more locally invasive, more likely to metastasize and has a recurrence rate of 12 - 51% following surgical excision. While BSC most frequently presents in the head and neck, it can also occur in gynecological cases and this subset of cases has not been studied in literature. In order to more thoroughly understand the distinguishing features and epidemiological trends of this rare cancer, the National Cancer Database (NCDB) was analyzed to determine demographic factors in patients diagnosed with cases of BSC in the breast, vagina and vulva. Methods: The National Cancer Database (NCDB) was utilized to complete a retrospective cohort analysis from 2004 – 2020 that included all patients with histologically-confirmed gynecological cases of BSC (N = 211). Descriptive statistics were analyzed for demographic factors including age, sex, race, income level, insurance status, and Charlson-Deyo score. Results: Between 2004 and 2020 there were 211 identified gynecological cases of BSC. The average age of diagnosis was 71.1 years (SD = 14.6, range = 22 – 90 years) with the majority being non-Hispanic (89.1%) and White (86.3%). The primary site in the vast majority of cases was the vulva (88.6%) and remaining cases originated in other female organs including the breast, vagina and cervix (11.4%). Despite the older age of diagnosis, the majority of individuals (72.0%) had Charlson-Deyo comorbidity scores of 0. The greatest proportion of patients (38.8%) were in the top quartile of household income ( &gt; $74,063) with 15.7% in the lowest income quartile ( &lt; $46,277). Additionally, most patients were insured by Medicare (64.9%) which aligns with the older age of diagnosis. Conclusions: Classifying and fully understanding BSC has proved difficult due to the challenge of differentiating it from other forms of basal cell carcinoma. To further the overall understanding of this aggressive cancer and those that it impacts, this study specifically focuses on a unique subset of BSC cases that have not been well studied. To the best of our knowledge, this is the first NCDB analysis on gynecological cases of BSC. The majority of BSC patients are non-Hispanic and White with an average age of over 70 years old which is supported by the finding that most patients rely on Medicare to fund their treatment. Additional research is needed to better understand the sociodemographic factors, treatments, and overall survival of patients with BSC in aberrant locations.
Efficacy and safety of lurbinectedin in elderly patients with relapsed SCLC.
Authors: Sophie Cousin, Luis G. Paz-Ares, Andrea Fülöp, Ildiko Horvath, Jose Manuel Manuel Trigo Perez, Jon Zugazagoitia, Laura Bonanno, Jose Antonio Lopez-Vilariño, Carmen Maria Kahatt, Cristian Marcelo Fernandez, Javier Gomez, Ali Hassan Zeaiter, Alejandro Navarro, Kostas N. Syrigos, Egbert Smit, Tudor-Eliade Ciuleanu, Alberto Chiappori, Rafael Lopez-Lopez, Benjamin Besse
Journal: Journal of Clinical Oncology (2023)

8591 Background: Relapsed SCLC is a difficult-to-treat disease. A considerable number of SCLC patients are elderly with associated fragility and numerous comorbidities. Accelerated approval from the US FDA of lurbinectedin (Zepzelca) 3.2 mg/m 2 q3wk as second-line therapy in metastatic small cell lung cancer (SCLC) was based on results from a phase 2 basket trial (NCT02454972) showing overall response rate of 35.2% and duration of response of 5.3 months. The ATLANTIS trial (NCT02566993) assessed the combination of lurbinectedin 2mg/m 2 / doxorubicin (DOX) 40 mg/m 2 as second-line treatment for SCLC vs. a control arm of topotecan/CAV. Methods: This post hoc analysis explores the efficacy and safety of lurbinectedin in relapsed SCLC patients ≥65 years included in both phase 2 basket (26 patients treated with lurbinectedin) and ATLANTIS (121 patients treated with lurbinectedin/DOX and 118 patients treated in the control arm) trials. This analysis did not include patients from the phase 2 basket trial with chemotherapy-free interval (CTFI) &lt; 30 days, as these patients were excluded in the ATLANTIS trial. Results: Median age was similar (72.5 in lurbinectedin basket vs. 69 in ATLANTIS lurbinectedin/DOX vs. 69 in ATLANTIS control arm), most were males (65.4% vs. 57.9% vs. 60.2%), with ECOG PS 1 (65.4% vs. 68.6% vs. 68.6%) and CNS involvement (7.7% vs. 10.7% vs. 15.3%). Median CTFI (days) was also similar (105.5 vs. 123 vs. 120). Median number of cycles was 4 vs. 6 vs. 4. Main efficacy and safety results are shown in the table. Treatment-related adverse events (AEs) were reported in 92.3%, 92.6% and 94.1% of patients, respectively (grade ≥3 in 50.0%, 59.5% and 81.4%). Conclusions: In elderly patients, lurbinectedin seems to be superior to the standard of care in terms of both efficacy (higher response rate and longer duration of response and overall survival) and safety (less associated hematological AEs), which reinforces its role as a treatment option in relapsed SCLC patients ≥65 years. Clinical trial information: NCT02454972 , NCT02566993 . [Table: see text]